The research program concerns biochemical studies of connective tissue macromolecules of cardiovascular structures. A previous report described the isolation of a proteoglycan from bovine aorta which contains chondroitin sulfates A and C and dermatan sulfate, but dissociative extraction of aorta by 3M MgCl and 4.OM guanidinium chloride resulted in isolation of only a portion of the glycosaminoglycans (GAG). An additional enzymatic digestion with elastase would release the remaining GAG. Other investigations using collagenase and elastase with appropriate inhibitors have suggested a specific relationship of certain GAG to the major connective tissue fibrous proteins, elastin and collagen, in the aorta. For example, heparan sulfate and dermatan sulfate appear to be firmly bound to elastin, and the chondroitin sulfates primarily to collagen. An experimental model of atherosclerosis was used to further study the connective tissue composition of the aorta in Rhesus monkeys; induction and regression of fatty streaks were affected by diet - fat-cholesterol and laboratory chow, respectively. Although a marked increase in hyaluronic acid and a decrease in chondroitin sulfate C occurred in regression, remodeling of the aorta was observed even after the animals were on a diet 64 weeks of chow (no cholesterol). A corollary study is exploring the interaction of lipoproteins and GAG and complexes in human atherosclerotic lesions. Other nutritional studies of subhuman primates are directed toward demonstrating intra- and interspecies differences in response to fat and cholesterol in the diet. Although different levels of lipid values were found in all six species studied, marked individual variability was observed in each of the species. Similarly, the effect of protein on the serum lipoproteins is being studied. As described before, GAG are used to quantitate serum lipoproteins and this method allows us to follow rapid lipoprotein responses in nutritional models being developed in primates to simulate human atherosclerosis.